Sun Yuan-Dong, Zhang Hao, Gong Xiao-Long, Li Yuan-Min, Han Ruiqin, Zhou Chun-Xiao, Han Jian-Jun
Xinjiang Medical University Affiliated Cancer Hospital, Urumqi, China.
Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, China.
Sci Rep. 2025 Jul 2;15(1):22699. doi: 10.1038/s41598-025-07557-7.
Metabolic Associated Fatty Liver Disease (MAFLD), previously known as Non-Alcoholic Fatty Liver Disease, is a growing global health issue associated with obesity, type 2 diabetes, and metabolic syndrome. This study investigates the potential of metformin, a common anti-diabetic drug, to slow the progression of MAFLD using a multi-omics approach. Male Wistar rats were fed a choline-deficient diet to induce MAFLD and treated with metformin through their drinking water for 48 weeks. We conducted a comprehensive analysis including liver histology, untargeted metabolomics, lipidomics, and gut microbiome profiling to assess the effects of metformin on liver and gut metabolic patterns. Metformin administration led to significant changes in gut microbiome diversity and the abundance of specific microbial species in MAFLD rats. Histological analysis showed that metformin-treated rats had reduced lipid accumulation and fibrosis in the liver compared to untreated MAFLD rats. Metabolomic and lipidomic analyses revealed that metformin corrected abnormal lipid metabolism patterns, reduced hepatic fat deposition, and influenced key metabolic pathways associated with MAFLD progression. Our findings suggest that metformin has a protective role against MAFLD by modulating gut microbiota and liver metabolism, thereby slowing the progression of hepatic fibrosis. This study provides insights into the therapeutic potential of metformin for MAFLD by addressing metabolic pattern disorders and abnormal changes in gut microbial diversity, highlighting its impact on lipid metabolism and gut-liver axis interactions.
代谢相关脂肪性肝病(MAFLD),以前称为非酒精性脂肪性肝病,是一个日益严重的全球健康问题,与肥胖、2型糖尿病和代谢综合征相关。本研究使用多组学方法研究了常见抗糖尿病药物二甲双胍减缓MAFLD进展的潜力。给雄性Wistar大鼠喂食缺乏胆碱的饮食以诱导MAFLD,并通过饮用水用二甲双胍治疗48周。我们进行了全面分析,包括肝脏组织学、非靶向代谢组学、脂质组学和肠道微生物组分析,以评估二甲双胍对肝脏和肠道代谢模式的影响。给予二甲双胍导致MAFLD大鼠肠道微生物组多样性和特定微生物种类丰度发生显著变化。组织学分析表明,与未治疗的MAFLD大鼠相比,用二甲双胍治疗的大鼠肝脏中的脂质积累和纤维化减少。代谢组学和脂质组学分析显示,二甲双胍纠正了异常的脂质代谢模式,减少了肝脏脂肪沉积,并影响了与MAFLD进展相关的关键代谢途径。我们的研究结果表明,二甲双胍通过调节肠道微生物群和肝脏代谢对MAFLD具有保护作用,从而减缓肝纤维化的进展。本研究通过解决代谢模式紊乱和肠道微生物多样性异常变化,深入了解了二甲双胍对MAFLD的治疗潜力,突出了其对脂质代谢和肠-肝轴相互作用的影响。
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